SIRT7–SREBP1 restrains cancer cell metabolic reprogramming by upregulating IDH1
SIRT7–SREBP1 restrains cancer cell metabolic reprogramming by upregulating IDH1
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DOI：
10.1007/s42764-021-00031-4
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Fengting Su;Xiaolong Tang;Guo Li;A. Koeberle;Baohua Liu
中科院分区：
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作者：
Fengting Su;Xiaolong Tang;Guo Li;A. Koeberle;Baohua Liu
SIRT7在肿瘤发生和肿瘤进展中起关键作用；然而，人们对其潜在机制知之甚少。在这里，我们旨在确定SIRT7的下游靶点，以帮助描述其精确的功能。在这项研究中，我们证明SIRT7在各种癌细胞类型中对调节IDH1表达至关重要。有趣的是，SIRT7和IDH1水平在乳腺癌肺转移中均下调，可用于预测疾病进展和预后。从机制上讲，SIRT7增强了idh1的转录，这一过程是由SREBP1介导的。sirt7不足降低细胞α-酮戊二酸（IDH1的代谢产物），抑制脂肪生成和糖异生。此外，α-酮戊二酸降低会增加hf1 α蛋白水平，从而促进糖酵解。这种作用使癌细胞易于沃伯格效应，进行快速增殖。总的来说，SIRT7-IDH1轴调节癌细胞代谢重编程，因此可能作为治疗干预的一个点。
SIRT7 plays critical roles in tumorigenesis and tumor progression; however, the underlying mechanisms are poorly understood. Here, we aimed to identify downstream targets of SIRT7 to help delineate its precise function. In this study, we demonstrate that SIRT7 is essential to regulate IDH1 expression in various cancer cell types. Interestingly, both SIRT7 and IDH1 levels are downregulated in breast cancer lung metastases and are useful for predicting disease progression and prognosis. Mechanistically, SIRT7 enhancesIDH1transcription, and this process is mediated by SREBP1.SIRT7insufficiency reduces cellular α-ketoglutarate, a metabolite product of IDH1, and suppresses lipogenesis and gluconeogenesis. Moreover, α-ketoglutarate decline increases HIF1α protein levels and, thus, promotes glycolysis. This effect permits cancer cells to facilitate Warburg effect and undergo fast proliferation. Overall, the SIRT7–IDH1 axis regulates cancer cell metabolic reprogramming and, thus, might serve as a point of therapeutic intervention.